EP1475094B8 - Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use - Google Patents

Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use Download PDF

Info

Publication number
EP1475094B8
EP1475094B8 EP03010184A EP03010184A EP1475094B8 EP 1475094 B8 EP1475094 B8 EP 1475094B8 EP 03010184 A EP03010184 A EP 03010184A EP 03010184 A EP03010184 A EP 03010184A EP 1475094 B8 EP1475094 B8 EP 1475094B8
Authority
EP
European Patent Office
Prior art keywords
substituted
alkyl
unsubstituted
cycloalkyl
arylalkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP03010184A
Other languages
German (de)
French (fr)
Other versions
EP1475094A1 (en
EP1475094B1 (en
Inventor
Daniela Moravcova
Libor Havlicek
Vladimir Krystof
Rene Lenobel
Pavla Binarova
Petra Mlejnek
Borek Vojtesek
Stjepan Uldrijan
Thomas SCHMÜLLING
Miroslav Strnad
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
UNIVERSITA PALACKEHO V OLOMOUCI
Institute of Experimental Botany Academy CAS
Original Assignee
Universita Palackeho v Olomouci
Institute of Experimental Botany Academy CAS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AT03010184T priority Critical patent/ATE475421T1/en
Application filed by Universita Palackeho v Olomouci, Institute of Experimental Botany Academy CAS filed Critical Universita Palackeho v Olomouci
Priority to DK03010184.4T priority patent/DK1475094T3/en
Priority to ES03010184T priority patent/ES2351624T3/en
Priority to DE60333546T priority patent/DE60333546D1/en
Priority to EP03010184A priority patent/EP1475094B8/en
Priority to PCT/EP2004/004855 priority patent/WO2004098608A1/en
Priority to US10/555,528 priority patent/US20070167466A1/en
Priority to CA2524344A priority patent/CA2524344C/en
Publication of EP1475094A1 publication Critical patent/EP1475094A1/en
Publication of EP1475094B1 publication Critical patent/EP1475094B1/en
Application granted granted Critical
Publication of EP1475094B8 publication Critical patent/EP1475094B8/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Abstract

The invention relates to 3-, 7-disubstituted pyrazoloÄ4,3-dÜpyrimidines represented by the general formula I <CHEM> and pharmaceutically acceptable salts thereof, wherein R3 is selected from the group consisting of alkyl, cycloalkyl,, cycloalkyl alkyl, cycloheteroalkyl alkyl, cycloheteroalkyl, aryl, heterocycle, heteroaryl, arylalkyl, heteroarylalkyl, and heteroalkyl, wherein each of the groups may optionally be substituted, R7 is selected from the group consisting of halogen, hydroxyl, hydroxylamino, amino, carboxyl, cyano, nitro, amido, sulfo, sulfamido, carbamino, unsubstituted or substituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroarylakyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted cycloheteroalkyl alkyl; R7'-X- wherein X is an -NH-, -N(alkyl)-, -O- or -S- moiety and R7' is selected from the group consisting ofH, alkyl, cycloalkyl, aryl, alkylcycloalkyl, arylalkyl, heterocycle, heterocyclealkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted arylalkyl, substituted heterocycle, substituted heteroaryl, substituted heteroarylalkyl, substituted heteroalkyl, substituted cycloalkyl alkyl and substituted cycloheteroalkyl alkyl, wherein the groups are preferably substituted by more than one halogen, hydroxyl, amino, mercapto, carboxyl, cyano, nitro, amido, sulfo, sulfamido, carbamino, alkyl, alkoxy, and substituted alkyl group <IMAGE>
EP03010184A 2003-05-06 2003-05-06 Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use Expired - Lifetime EP1475094B8 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
DK03010184.4T DK1475094T3 (en) 2003-05-06 2003-05-06 Pyrazolo [4,3-d] pyrimidines, processes for their preparation and their use
ES03010184T ES2351624T3 (en) 2003-05-06 2003-05-06 PIRAZOLO [4,3-D] PYRIMIDINS, PROCEDURE FOR PREPARATION AND USE.
DE60333546T DE60333546D1 (en) 2003-05-06 2003-05-06 Pyrazolo4,3-duplex pyrimidines, process for their preparation and their use
EP03010184A EP1475094B8 (en) 2003-05-06 2003-05-06 Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use
AT03010184T ATE475421T1 (en) 2003-05-06 2003-05-06 PYRAZOLOA4,3-DÜPYRIMIDINES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE
US10/555,528 US20070167466A1 (en) 2003-05-06 2004-05-06 "Pyrazolo [4,3-d]pyrimidines, processes for their preparation and methods of use"
PCT/EP2004/004855 WO2004098608A1 (en) 2003-05-06 2004-05-06 Pyrazolo [4, 3-d]pyrimidines, processes for their preparation and methods of use
CA2524344A CA2524344C (en) 2003-05-06 2004-05-06 Pyrazolo [4, 3-d]pyrimidines, process for their preparation and methods of use

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP03010184A EP1475094B8 (en) 2003-05-06 2003-05-06 Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use

Publications (3)

Publication Number Publication Date
EP1475094A1 EP1475094A1 (en) 2004-11-10
EP1475094B1 EP1475094B1 (en) 2010-07-28
EP1475094B8 true EP1475094B8 (en) 2011-01-12

Family

ID=32981816

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03010184A Expired - Lifetime EP1475094B8 (en) 2003-05-06 2003-05-06 Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use

Country Status (8)

Country Link
US (1) US20070167466A1 (en)
EP (1) EP1475094B8 (en)
AT (1) ATE475421T1 (en)
CA (1) CA2524344C (en)
DE (1) DE60333546D1 (en)
DK (1) DK1475094T3 (en)
ES (1) ES2351624T3 (en)
WO (1) WO2004098608A1 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1599468T3 (en) 2003-01-14 2008-02-04 Arena Pharm Inc 1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prevention and treatment of disorders associated therewith such as diabetes and hyperglycemia
AR045047A1 (en) 2003-07-11 2005-10-12 Arena Pharm Inc ARILO AND HETEROARILO DERIVATIVES TRISUSTITUIDOS AS MODULATORS OF METABOLISM AND PROFILAXIS AND TREATMENT OF DISORDERS RELATED TO THEMSELVES
EP2287166A3 (en) 2003-07-14 2011-06-22 Arena Pharmaceuticals, Inc. Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto
JP4845730B2 (en) 2003-07-17 2011-12-28 プレキシコン，インコーポレーテッド PPAR active compounds
DOP2006000010A (en) 2005-01-10 2006-07-31 Arena Pharm Inc PROCEDURE TO PREPARE AROMATIC ETERES
MY148521A (en) 2005-01-10 2013-04-30 Arena Pharm Inc Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto
US7932257B2 (en) * 2005-07-22 2011-04-26 Sunesis Pharmaceuticals, Inc. Substituted pyrazolo[4,3-d]pyrimidines as aurora kinase inhibitors
EP2170340B1 (en) * 2007-06-21 2016-02-24 Neuronascent, INC. Methods and compositions for stimulating neurogenesis and inhibiting neuronal degeneration using isothiazolopyrimidinones
KR101483215B1 (en) * 2010-01-29 2015-01-16 한미약품 주식회사 Bicyclic heteroaryl derivatives having inhibitory activity for protein kinases
SG188548A1 (en) 2010-09-22 2013-04-30 Arena Pharm Inc Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2014126580A1 (en) * 2013-02-15 2014-08-21 Dow Agrosciences Llc Pesticidal compositions and processes related thereto
EP3242666A1 (en) 2015-01-06 2017-11-15 Arena Pharmaceuticals, Inc. Methods of treating conditions related to the s1p1 receptor
CZ307147B6 (en) 2015-05-14 2018-02-07 Ústav experimentální botaniky AV ČR, v. v. i. 5-Substituted 7-[4-(2-pyridyl)phenylmethylamino]-3-isopropylpyrazolo [4,3-d]pyrimidines, their use as pharmaceuticals, and pharmaceutical preparations
JP6838744B2 (en) 2015-06-22 2021-03-03 アリーナ ファーマシューティカルズ， インコーポレイテッド (R) -2- (7- (4-cyclopentyl-3- (trifluoromethyl) benzyloxy) -1,2,3,4-tetrahydrocyclopenta [b] indole-for use in S1P1 receptor-related disorders Crystalline L-arginine salt of 3-yl) acetic acid (Compound 1)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1530747A (en) * 1922-05-20 1925-03-24 Frank B Wyatt Motion-picture machine
GB1530747A (en) * 1976-04-05 1978-11-01 Massachusetts Inst Technology Pharmaceutical composition
US4282361A (en) * 1978-03-16 1981-08-04 Massachusetts Institute Of Technology Synthesis for 7-alkylamino-3-methylpyrazolo [4,3-d]pyrimidines
CZ27399A3 (en) * 1999-01-26 2000-08-16 Ústav Experimentální Botaniky Av Čr Substituted nitrogen heterocyclic derivatives process of their preparation, the derivatives employed as medicaments, pharmaceutical composition and a compound pharmaceutical preparation in which these derivatives are comprised as well as use of these derivatives for preparing medicaments
WO2001018170A2 (en) * 1999-08-26 2001-03-15 Plant Research International B.V. Conditional inhibition of vegetative propagation
DE10060388A1 (en) * 2000-12-05 2002-06-06 Merck Patent Gmbh Use of pyrazolo [4,3-d] pyrimidines

Also Published As

Publication number Publication date
EP1475094A1 (en) 2004-11-10
DE60333546D1 (en) 2010-09-09
ES2351624T3 (en) 2011-02-08
EP1475094B1 (en) 2010-07-28
ATE475421T1 (en) 2010-08-15
WO2004098608A1 (en) 2004-11-18
DK1475094T3 (en) 2010-11-22
US20070167466A1 (en) 2007-07-19
CA2524344A1 (en) 2004-11-18
CA2524344C (en) 2012-03-13

Similar Documents

Publication Publication Date Title
EP1475094B8 (en) Pyrazolo[4,3-D]pyrimidines, process for their preparation and methods of use
MX2007012951A (en) Process for preparing pyrido[2,3-d]pyrimidin-7-one and 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1h)-one derivatives.
MY126862A (en) Purine derivatives inhibitors of tyrosine protein kinase syk
NO20055510L (en) 2-alkynyl and 2-alkenylpyrazolo [4,3-E] -1,2,4-triazolo [1,5-C] pyrimidine-adenosine A2A receptor antagonists
DE60000611T2 (en) 4-OXO-4,7-DIHYDRO-THIENO [2,3-B] PYRIDINE-5-CARBOXAMIDE AS AN ANTIVIRAL AGENT
WO2005037825A3 (en) Protein kinase inhibitors
CA2438646A1 (en) Pyrimidine derivatives for inhibition of cell-proliferation
TW200736257A (en) Aryl-isoxazol-4-yl-imidazo[1,2-a]pyridine derivatives
WO2007051081B1 (en) Methods and compounds for preparing cc-1065 analogs
TW200734328A (en) Aryl-isoxazolo-4-yl-imidazo [1,5-a] pyridine derivatives
CA2369070A1 (en) 1,4-benzothiazepine-1,1-dioxide derivatives substituted by sugar radicals, methods for the production thereof, medicaments containing these compounds and the use thereof
RS20050572A (en) Nitrogen-substituted hexahydropyrazino(1,2-a)pyrimidine – 4,7-dione derivatives, method for the production and use thereof as medicaments
HUP0303016A2 (en) Xanthine phosphodiesterase v inhibitors, process for their preparation and pharmaceutical compositions containing them and their use
EA200600973A1 (en) PYRIDO [2,3-d] PYRIMIDIN-2,4-DIAMINS AS PDE 2 INHIBITORS
TW200640900A (en) 1-(2h)-isoquinolone derivative
EA200701991A1 (en) NEW IMIDAZO DERIVATIVES [1,5-a] PYRIDINES, METHOD OF THEIR RECEPTION AND CONTAINING THEIR PHARMACEUTICAL COMPOSITIONS
DK1348707T3 (en) Pyrazolo [4,3-d] pyrimidines, methods for their preparation and their therapeutic use
WO2007022502A3 (en) Bridged n-cyclic sulfonamido inhibitors of gamma secretase
NO20070837L (en) Pyrido-pyrido pyrimidine derivatives, their preparation and therapeutic application for the treatment of cancer.
CA2533685A1 (en) Nitrogen-containing fused heterocyclic carboxylic acid compounds
WO2003082861A3 (en) Morpholinyl-urea derivatives for use of the treatment of inflammatory diseases
DE50310080D1 (en) 3-SUBSTITUTED 3,4-DIHYDRO-THIENOi2,3-D PYRIMIDIN-4-ONE DERIVATIVES, THEIR PREPARATION AND USE
CA2370830A1 (en) Use of 2,4-diamino-3-hydroxycarboxylic acid derivatives as proteasome inhibitors
WO2004075858A3 (en) Flavone acetic acid analogs and methods of use thereof
WO2003045940A3 (en) Benzazepine derivatives and their use as 5-ht ligands

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL LT LV MK

17P Request for examination filed

Effective date: 20050504

AKX Designation fees paid

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

RTI1 Title (correction)

Free format text: PYRAZOLO??4,3-D PYRIMIDINES, PROCESS FOR THEIR PREPARATION AND METHODS OF USE

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RIC1 Information provided on ipc code assigned before grant

Ipc: C07D 487/04 20060101ALI20091106BHEP

Ipc: A61K 31/505 20060101AFI20091106BHEP

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

RTI1 Title (correction)

Free format text: PYRAZOLO(4,3-D)PYRIMIDINES, PROCESS FOR THEIR PREPARATION AND METHODS OF USE

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: USTAV EXPERIMENTALNI BOTANIKY AKADEMIE VED CESKE R

Owner name: UNIVERSITA PALACKEHO V OLOMOUCI

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REF Corresponds to:

Ref document number: 60333546

Country of ref document: DE

Date of ref document: 20100909

Kind code of ref document: P

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: NL

Ref legal event code: T3

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

RAP2 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: UNIVERSITA PALACKEHO V OLOMOUCI

Owner name: USTAV EXPERIMENTALNI BOTANIKY AV CR, V.V.I. (

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: PA MATTHIAS SCHAEFER

Ref country code: CH

Ref legal event code: PK

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Effective date: 20110127

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20101028

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20101129

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20101029

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20110429

REG Reference to a national code

Ref country code: CH

Ref legal event code: PCAR

Free format text: PATENTANWALT MATTHIAS W. SCHAEFER;AM SCHANZENGRABEN 27;8002 ZUERICH (CH)

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 60333546

Country of ref document: DE

Effective date: 20110429

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110531

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DK

Payment date: 20120516

Year of fee payment: 10

Ref country code: IE

Payment date: 20120522

Year of fee payment: 10

Ref country code: CH

Payment date: 20120522

Year of fee payment: 10

Ref country code: DE

Payment date: 20120512

Year of fee payment: 10

Ref country code: NL

Payment date: 20120523

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20120522

Year of fee payment: 10

Ref country code: GB

Payment date: 20120522

Year of fee payment: 10

Ref country code: FR

Payment date: 20120608

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20120523

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20120525

Year of fee payment: 10

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110506

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100728

REG Reference to a national code

Ref country code: NL

Ref legal event code: V1

Effective date: 20131201

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: SE

Ref legal event code: EUG

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20130506

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130507

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20131203

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130531

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130531

REG Reference to a national code

Ref country code: DK

Ref legal event code: EBP

Effective date: 20130531

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 60333546

Country of ref document: DE

Effective date: 20131203

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130506

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20131201

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20140131

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130531

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130506

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130506

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130531

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20140606

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130507